Malaria is one of the most important mosquito-borne diseases, and Anopheles sinensis mosquito is the predominant malaria vector in China. Insecticide-impregnated bed nets and indoor-residual spray are the most effective means of mosquito vector control. The insecticides of choice for bed nets and indoor-residual spray are pyrethroids because of their high efficacy, rapid rate of knockdown, and low mammalian toxicity. However, pyrethroid resistance has been reported in An. sinensis populations throughout China in bioassays, and this has significantly hindered the effectiveness of the recently proposed malaria elimination program in China. Early detection of insecticide resistance and resistance surveillance are critical to resistance management and to the rational use of insecticides. The long-term goal of this research is to elucidate the molecular mechanisms of pyrethroid resistance in An. sinensis mosquitoes, and to use the knowledge to develop field-applicable and cost-effective resistance detection methods. This application will test central hypothesis that combination of genetic mapping, transcriptome sequencing and functional genomics approaches will greatly improve our understanding of molecular mechanisms of An. sinensis mosquito resistance to deltamethrin. The three specific aims are: 1) to identify the major loci for resistance to deltamethrin in An. sinensis using quantitative trait loci mapping technique, 2) to conduct transcriptome analysis between deltamethrin-susceptible and resistant An. sinensis populations, and 3) to determine the association between organismal deltamethrin resistance in natural An. sinensis populations and molecular polymorphisms in knockdown resistance (kdr) gene and metabolic detoxification genes. Combination of genetic mapping and transcriptome analysis and field medical entomology will allow identification and a comprehensive evaluation of the contribution of different mechanisms to pyrethroid resistance. This research will significantly enhance the understanding of resistance to pyrethroid insecticides in An. sinensis mosquitoes, and lays an important foundation for developing new resistance diagnostic methods for the most important malaria vector in China. PUBLIC HEALTH RELEVANCE: Insecticide resistance is the biggest obstacle to successful control of malaria vectors in China. This project will improve the understanding of the genetic mechanisms of resistance to pyrethroid insecticide in mosquitoes, and lay an important foundation for developing novel diagnosis methods.